Zhang Yijian, Li Li, Ye Zhihui, Zhang Lei, Yao Ninghua, Gai Ling
Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China.
Department of Oncology, Huaian Hospital, Huaian, China.
Ann Transl Med. 2021 Oct;9(20):1554. doi: 10.21037/atm-21-4712.
Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck malignant tumors. As the early symptoms of HNSCC are not obvious, and it is prone to recurrence and metastasis, making the overall survival (OS) rate of patients very low. Existing studies have shown m6A methylation plays a crucial role in various cancers, but it is rarely studied in HNSCC. This study aimed to explore the expression of m6A methylation-related genes in HNSCC and its correlation with prognosis, and to explore its relationship with immune infiltration.
The gene expression data of HNSCC patient tumor samples (tumor =510) and adjacent normal tissue samples (normal =50) were extracted from The Cancer Genome Atlas (TCGA) database, and the expression characteristics of m6A regulatory factors were described. Kaplan-Meier survival analysis was used to analyze the relationship between m6A regulatory factors and OS and disease-specific survival (DSS). Least absolute shrinkage and selection operator (LASSO) regression was used to construct the m6A regulatory factor-HNSCC risk prediction model. In addition, the relationship between m6A methylation-related genes and tumor immune infiltration were discussed.
The differential expression of 20 genes were identified by TCGA, and 18 genes (, , , , , , , , , , , , , , , , , and ) were overexpressed in HNSCC. The survival rate of different gene expression levels was different. The high expression of and indicated better OS. Furthermore, for DSS, increased expression of was also correlated with better clinical outcomes (P<0.05). At the same time, we drew a 3-gene risk score model in the TCGA-HNSCC cohort, and the survival curve showed compared with low-risk patients, high-risk patients had significantly worse OS (P<0.05). Gene enrichment analysis showed EPITHELIAL_MESENCHYMAL_TRANSITIO, MTORC1_SIGNALING, MYC_TARGETS_V1, MYC_TARGETS_V2, MYOGENESIS pathways, high TP53 mutations, and suppressive immunity were related to the high-risk group. The low-risk group was related to ALLOGRAFT_REJECTION, COMPLEMENT, IL6_JAK_STAT3_SIGNALING, INTERFERON_ALPHA_RESPONSE, INTERFERON_GAMMA_RESPONSE pathways, low TP53 mutations, and active immunity.
The m6A methyltransferase-related genes can predict the prognosis of HNSCC and are related to immune infiltration.
头颈部鳞状细胞癌(HNSCC)占头颈部恶性肿瘤的90%。由于HNSCC的早期症状不明显,且易于复发和转移,导致患者的总生存率(OS)非常低。现有研究表明,m6A甲基化在各种癌症中起着关键作用,但在HNSCC中的研究很少。本研究旨在探讨m6A甲基化相关基因在HNSCC中的表达及其与预后的相关性,并探讨其与免疫浸润的关系。
从癌症基因组图谱(TCGA)数据库中提取HNSCC患者肿瘤样本(肿瘤=510)和邻近正常组织样本(正常=50)的基因表达数据,并描述m6A调控因子的表达特征。采用Kaplan-Meier生存分析来分析m6A调控因子与OS和疾病特异性生存(DSS)之间的关系。使用最小绝对收缩和选择算子(LASSO)回归构建m6A调控因子-HNSCC风险预测模型。此外,还讨论了m6A甲基化相关基因与肿瘤免疫浸润之间的关系。
通过TCGA鉴定出20个基因的差异表达,其中18个基因(,,,,,,,,,,,,,,,,,和)在HNSCC中过表达。不同基因表达水平的生存率不同。和的高表达表明OS较好。此外,对于DSS,的表达增加也与更好的临床结果相关(P<0.05)。同时,我们在TCGA-HNSCC队列中绘制了一个三基因风险评分模型,生存曲线显示,与低风险患者相比,高风险患者的OS明显更差(P<0.05)。基因富集分析表明,上皮-间质转化、MTORC1信号传导、MYC靶点V1、MYC靶点V2、肌生成途径、高TP53突变和免疫抑制与高风险组相关。低风险组与同种异体移植排斥、补体、IL6-JAK-STAT3信号传导、干扰素α反应、干扰素γ反应途径、低TP53突变和主动免疫相关。
m6A甲基转移酶相关基因可以预测HNSCC的预后,并与免疫浸润有关。